IDDF2024-ABS-0208 No resistance to tenofovir alafenamide (TAF) in adult, HBeAg-positive and HBeAg-negative participants with chronic hepatitis B infection treated with TAF for up to 8 years

<h3>Background</h3> TAF resistance has not been detected after up to three years of treatment in CHB patients. Here, we report results from annual resistance surveillance from years 3 through 8 of TAF treatment. <h3>Methods</h3> Two randomized, double-blind (DB), active-controlled trials to evaluate TAF treatment of hepatitis e antigen (HBeAg)-negative and HBeAg-positive participants with CHB were conducted over 8 years (384 weeks). Sequence analysis of the pol/RT region was attempted for any participant who experienced a viral breakthrough, viral blip, or persistent viremia with HBV DNA ≥69 IU/mL at annual intervals and for any participant who discontinued the study drug with HBV DNA ≥69 IU/mL. Participants that developed substitutions at conserved pol/RT sites or at polymorphic residues (if observed in ≥2 participants within the study) were also phenotyped against TAF. <h3>Results</h3> Out of 1298 participants, the percentage of participants who qualified for resistance analysis annually from Week 144 to Week 384 remained low (range 1.7 – 8.4%). Among those qualifying for sequencing, the proportions with persistent viremia progressively declined with time, with only 3 participants being persistently viremic by Year 8. The viral load of these 3 participants at baseline was &gt;10⁸ log10 IU/mL and declined over time but did not reach 69 IU/mL. During the 5-year open-label period where all participants received TAF, conserved site substitutions in the HBV viral pol/RT were observed in 13 participants. <h3>Conclusions</h3> Overall, no resistance to TAF was detected in adult CHB participants with positive or negative HBeAg who received TAF therapy for up to 8 years.